PDGF-Rβ is a receptor tyrosine kinase implicated in fibrotic and oncologic disease, and represents a potentially valuable molecular imaging target. The ability to qualitatively or quantitatively visualize PDGF-Rβ, either in vivo or in vitro, confers upon researchers and clinicians important diagnostic and treatment tools. For example, the ability to visually identify liver-associated diseases, such as liver fibrosis, cirrhosis, or abnormal liver function. The ability to measure expression patterns of PDGF-Rβ in vivo in patients with such conditions would aid clinicians and researchers in diagnosing, prognosing, and treating liver-associated disease conditions.
Naturally occurring Staphylococcal protein A comprises domains that form three-helix structures that bind to the Fc region of IgG. The Z domain of the 58-residue polypeptide derived from the B domain of staphylococcal protein A retains binding.
Certain polypeptides, derived from the Z-domain of protein A, contain a scaffold composed of three α-helices connected by loops. Certain residues situated on two of these helices constitute a binding site for the Fc-portion of IgG. According to the terminology used in the field of protein engineering, the binding surface is a surface situated on a scaffold. Thus, the present scaffold is a three-helical bundle protein domain. Alternative binder molecules were created by substituting 13 surface exposed amino acid residues situated on helices 1 and 2, to replace the ability to bind the Fc-portion of IgG with binding to other molecules.